Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH / BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH / BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH / BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH / BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

Prenatal exposure to maternal Toxoplasma gondii (T. gondii) IgG antibody titer has been associated previously with an increased risk of offspring schizophrenia (SZ) and cognitive impairment. We examined maternal T gondii, offspring bipolar disorder (BP) and childhood cognition using a population based birth cohort. Maternal sera, drawn in the third trimester, were analyzed for T. gondii IgG antibody titer, and offspring cognition at ages 5 and 9-11 was measured with the Peabody Picture Vocabulary Test (PPVT) and the Raven Matrices (Raven). Raw scores were standardized and the ages combined. Potential cases with BP from the cohort were identified by database linkages. This protocol identified 85 cases who were matched 1:2 to controls. Maternal T. gondii IgG was not associated with the risk of BP in offspring. Neither moderate [HR = 1.43 (CI: 0.49, 4.17)] nor high IgG titer [HR=1.6 [CI: 0.74, 3.48)] were associated with offspring BP. Associations were not observed between maternal T gondii and BP with psychotic features or BP type 1. In addition, maternal T gondii was not associated with childhood cognition. Our study suggests that T. gondii may be specific to SZ among major psychotic disorders, though further studies with larger sample sizes are required. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Background. Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies.
Method. Electronic and manual searches and rigorous quality assessment yielded 21 studies that included an objective assessment of individual-level prenatal maternal infection and standardized psychotic diagnoses in adult offspring. Methodological differences between studies necessitated a descriptive review.
Results. Results for prenatal maternal non-specific bacterial, respiratory or genital and reproductive infection differed between studies, which reported up to a two-to fivefold increased risk of schizophrenia. Evidence for herpes simplex virus type 2 (HSV-2) and Toxoplasma gondii was mixed; some studies reported up to a doubling of schizophrenia risk. Prenatal HSV-1 or cytomegalovirus (CMV) infections were not associated with increased risk. Exposure to influenza or other infections during early pregnancy may be more harmful than later exposure. Increased proinflammatory cytokines during pregnancy were also associated with risk. Prenatal infection was associated with structural and functional brain abnormalities relevant to schizophrenia.
Conclusions. Prenatal exposure to a range of infections and inflammatory responses may be associated with risk of adult schizophrenia. Larger samples, mediation and animal models should be used to investigate whether there is a 'sensitive period' during development, and the effects of prenatal infections on neurodevelopment. Inclusion of genetic and immunological information should help to elucidate to what extent genetic vulnerability to schizophrenia may be explained by vulnerability to infection.

Accumulating evidence suggests that maternal infection is a risk factor for schizophrenia. Prospective epidemiological studies indicate that maternal influenza, toxoplasmosis, and genital/reproductive infection are associated with this disorder in offspring. Preclinical models of maternal immune activation have supported the neurobiological plausibility of these microbes in schizophrenia. Previous studies suggest that treatment or prophylactic efforts targeting these and other infections could have significant effects on reducing the incidence of schizophrenia, given that they are common in the population and the effect sizes derived from epidemiological studies of these and other microbial pathogens and schizophrenia, to date, are not small. Fortunately, the occurrence of many of these infections can be reduced with relatively practical and inexpensive interventions that are scalable to large populations given adequate resources. Hence, in the present article, we focus on the potential for prevention of schizophrenia by control of infection, using these 3 categories of infection as examples. Lessons learned from previous successful public health efforts targeting these infections, including the relative advantages and disadvantages of these measures, are reviewed